-
Journal of Assisted Reproduction and... Apr 2015The associations between TNF-α and Interleukin gene polymorphisms and polycystic ovary syndrome (PCOS) risk have been studied in numerous epidemiological studies, but... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The associations between TNF-α and Interleukin gene polymorphisms and polycystic ovary syndrome (PCOS) risk have been studied in numerous epidemiological studies, but the results remain controversial. To investigate whether these polymorphisms facilitate susceptibility to PCOS, we conducted a comprehensive systematic review and meta-analysis.
METHODS
PubMed, Embase, Web of Science, Medline, CNKI, and Google Scholar were searched to obtain the genetic association studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (OR) with corresponding 95 % confidence intervals (CI) were used to assess the strengths of the associations. Funnel plots and Egger's tests were performed to test for possible publication bias. All statistical analyses were performed using Review Manager 5.2 and STATA11.0.
RESULTS
Eighteen articles were included in the final meta-analysis. The studies involved the following polymorphisms: TNF-α -308G > A, TNF-α -805C>T, TNF-α -1031 T>C, IL-1A -889C>T, IL-1B -511C>T, IL-1B +3953 T>C, IL-6 -174G>C, IL-10 -819C>T, IL-10 -1082A>G, IL-18 -607C>A, and IL-18 -137G>C. Our results show a significant association between PCOS risk and the TNF-α -1031 T>C polymorphism (For TC+CC vs. TT: OR=2.09, 95 % CI=1.58-2.76, p<0.0001. For C allele vs. T allele: OR=1.67, 95 % CI=1.33-2.09, p<0.0001) and between PCOS risk and the IL-6 -174>C polymorphism (For CC+GC vs. GG: OR=0.49, 95 % CI=0.25-0.95, p=0.03. For CC vs. GG: OR=0.48, 95 % CI=0.28-0.80, p=0.005. For C vs. G: OR=0.60, 95 % CI=0.42-0.87, p=0.007). No associations were found with the other genetic models.
CONCLUSION
The results of the meta-analysis suggest positive associations between the TNF-α -1031 T>C and IL-6 -174G>C polymorphisms and the risk of PCOS. No associations are found between PCOS risk and the TNF-α -308G>A, TNF-α -805C>T, IL-1A -889C>T, IL-1B -511C>T, IL-1B +3953C>T, IL-10 -819C>T, IL-10 -1082 A>G, IL-18 -607C>A, and IL-18 -137G>C polymorphisms. However, due to the heterogeneity and low quality of the studies related to PCOS polymorphisms in the meta-analysis, the results should be interpreted with caution. Future multi-ethnicity studies of homogeneous populations of PCOS patients with larger sample sizes and well-matched controls are needed.
Topics: Alleles; Female; Genetic Predisposition to Disease; Humans; Interleukins; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Tumor Necrosis Factor-alpha
PubMed: 25690158
DOI: 10.1007/s10815-015-0449-7 -
Medicine Mar 2018This meta-analysis aims to examine whether the MspI and Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer risk. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This meta-analysis aims to examine whether the MspI and Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer risk.
METHODS
Eligible case-control studies were identified dated until July 2017. Pooled odds ratios (ORs) were used to assess the strength of the association between the two variants and cervical cancer risk.
RESULTS
Thirteen studies were eligible (2148 cases and 2252 controls) concerning MspI polymorphism and 8 studies were eligible (1466 cases and 1690 controls) for Ile462Val polymorphism. MspI polymorphism seemed to result in cervical cancer risk in any genetic model (C allele vs T allele: OR = 1.44, 95% confidence interval [CI] = 1.16-1.79; heterozygous model: OR = 1.40, 95% CI = 1.08-1.82; homozygous model: OR = 2.22, 95% CI = 1.48-3.33, dominant model: OR = 1.50, 95% CI = 1.14-1.98 and recessive model: OR = 1.80, 95% CI = 1.35-2.41); similar significantly increased risk was found among Caucasians and Asians. Ile462Val polymorphism was associated with elevated cervical cancer risk (Val allele vs Ile allele: OR = 1.85, 95% CI = 1.27-2.67; heterozygous model: OR = 1.42, 95% CI = 1.28-1.61; homozygous model: OR = 2.94, 95% CI = 1.15-7.54; dominant model: OR = 2.00, 95% CI = 1.33-3.00); this finding was replicated upon Caucasian population.
CONCLUSION
This meta-analysis demonstrated that polymorphisms in MspI and Ile462Val of CYP1A1 were risk factors for developing cervical cancer.
Topics: Alleles; Asian People; Cytochrome P-450 CYP1A1; Female; Genetic Predisposition to Disease; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors; Uterine Cervical Neoplasms; White People
PubMed: 29595663
DOI: 10.1097/MD.0000000000010210 -
Journal of Alzheimer's Disease : JAD 2021The global race-dependent association of Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The global race-dependent association of Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations.
OBJECTIVE
This study aims to determine how race and APOE genotype affect the risks for AD.
METHODS
We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes.
RESULTS
The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOEɛ4 was a risk factor for AD, whereas APOEɛ2 protected against it. The effects of APOEɛ4 and ɛ2 on AD risk were distinct in various races, and they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOEɛ4/ɛ4 and lower frequency of APOEɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races.
CONCLUSION
Our meta-analysis suggests that the association of APOE genotypes and AD differ among races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.
Topics: Alleles; Alzheimer Disease; Apolipoprotein E2; Apolipoprotein E4; Apolipoproteins E; Genotype; Humans; Racial Groups
PubMed: 34334408
DOI: 10.3233/JAD-210549 -
Drug Metabolism Letters 2021Cytochrome P450 (CYP) contributes to a huge collection of medicinal products' Phase I metabolization. We aimed to summarize and investigate the current evidence...
BACKGROUND
Cytochrome P450 (CYP) contributes to a huge collection of medicinal products' Phase I metabolization. We aimed to summarize and investigate the current evidence regarding the frequency of CYP2D6, CYP2C9, CYP2C19, and MDR1 in Saudi Arabia.
METHODS
A computerized search in four databases was done using the relevant keywords. The screening process was done in two steps; title and abstract screening and full-text screening. Data of demographic and characteristics of included studies and patients were extracted and tabulated.
RESULTS
Ten studies were eligible for our criteria and were included in this systematic review. The age of participants ranged between 17-65 years. Only two subjects showed PM phenotype of CYP2C19 in the Saudi population. The most frequent alleles were CYP2C19*1 (62.9%), CYP2C19*2 (11.2%-32%), and CYP2C19*17 (25.7%). The CYP2C19 was observed in 97 cases of extensive metabolizing (EM) phenotype CYP2C19. Concerning the CYP2C9, the most frequent alleles were CYP2C9*1 and CYP2C9*2, and the most frequent genotype was CYP2C9*1*1. The CYP2D6*41 allele and C1236T MDR1 were the most frequent allele in this population.
CONCLUSION
The current evidence suggests that Saudi resembled European in the frequency of CYP2C19, Caucasians in both the incidence of CYP2C9 and CYP2C19, and the absence of CYP2C19. The CYP2D6*41 allele frequency in Saudi is relatively high. We recommend further research to evaluate the basic and clinical relevance of gene polymorphism in such ethnicity.
Topics: ATP Binding Cassette Transporter, Subfamily B; Adolescent; Adult; Aged; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2D6; Cytochrome P-450 Enzyme System; Gene Frequency; Genetics, Population; Genotype; Humans; Middle Aged; Polymorphism, Genetic; Saudi Arabia; Young Adult
PubMed: 32703145
DOI: 10.2174/1872312814666200722122232 -
Journal of Clinical Pharmacy and... Jun 2018Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions that can be induced by phenytoin (PHT). CYP2C9*3 is the key... (Meta-Analysis)
Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions that can be induced by phenytoin (PHT). CYP2C9*3 is the key enzyme in PHT metabolism. The aim of this meta-analysis was to evaluate the association between CYP2C9*3 and PHT-induced SJS/TEN.
METHODS
An extensive search was performed in multiple databases, including the Cochrane Library, EMBASE, PubMed, OVID and EBSCO. Studies exploring the relationship between CYP2C9*3 and PHT-induced SJS and TEN were included. Odds ratios (ORs) with corresponding 95% confidence intervals (CI) were calculated for dichotomous data. Data analysis was performed using Review Manager (version 5.3).
RESULTS AND DISCUSSION
Four studies, with 117 PHT-induced SJS/TEN cases and 338 matched controls (PHT-tolerant patients) or 4231 population controls (general population), were identified. SJS and TEN were found to be significantly associated with the CYP2C9*3 allele, comparing both matched controls (OR, 8.93; 95% CI, 2.63-30.36; P = .0005) with substantial heterogeneity (I = 46%) and population controls (OR, 8.88; 95% CI, 5.01-15.74; P < .00001).
WHAT IS NEW AND CONCLUSION
A significant association between CYP2C9*3 and PHT-induced SJS/TEN was identified, especially in a Thai population. CYP2C9*3 is thus a credible predictive genetic marker of PHT-induced SJS/TEN. Further multicenter studies and large prospective observational studies are, however, still required to determine the influence of CYP2C*3 on blood levels of PHT and its metabolites, and their association with SJS/TEN.
Topics: Alleles; Anticonvulsants; Cytochrome P-450 CYP2C9; Genetic Markers; Humans; Phenytoin; Stevens-Johnson Syndrome
PubMed: 29274302
DOI: 10.1111/jcpt.12660 -
Pediatric Surgery International Oct 2016Some studies have been carried out to evaluate the association between SNP12 in estrogen receptor 1 and cryptorchidism, but the results remain inconsistent. We carried... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Some studies have been carried out to evaluate the association between SNP12 in estrogen receptor 1 and cryptorchidism, but the results remain inconsistent. We carried out a meta-analysis to explore the association between this polymorphism and cryptorchidism risk.
METHODS
All eligible studies were searched in PubMed, Web of Science, Embase and Cochrane Library. Pooled odds ratios, with 95 % confidence intervals, were assessed for the association using fixed- and random-effects models.
RESULTS
Overall, four case-control studies (363 cases, 415 controls) were included in the meta-analysis. No significant publication bias (P Begg = 0.308, P Egger = 0.288) was found. A allele of SNP12 in estrogen receptor 1 was protective factor to cryptorchidism in allele model, dominant genetic model and heterozygote comparison in Caucasians, but the result was turned out to be false positive by trial sequential analysis. However, A in allele model was risk factor to cryptorchidism in Asians (odds ratio 2.02, 95 % confidence interval 1.03-3.01, p = 0.946 for heterogeneity) and the result was turned out to be true positive by trial sequential analysis, even though there were merely two original studies.
CONCLUSIONS
The results of this meta-analysis suggest that A allele of SNP12 in estrogen receptor 1 may increase the risk of cryptorchidism in Asians. Meanwhile, further well-designed studies with large sample sizes are required to confirm the present findings, especially in Caucasians.
Topics: Adolescent; Alleles; Asian People; Child; Child, Preschool; Cryptorchidism; Estrogen Receptor alpha; Genetic Predisposition to Disease; Humans; Infant; Male; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 27376826
DOI: 10.1007/s00383-016-3926-x -
Journal of Sports Sciences Jan 2021The aim of this review was to assess the association of R577X and I/D polymorphisms with athlete status in football and determine which allele and/or genotypes are... (Meta-Analysis)
Meta-Analysis
The aim of this review was to assess the association of R577X and I/D polymorphisms with athlete status in football and determine which allele and/or genotypes are most likely to influence this phenotype via a meta-analysis. A comprehensive search identified 17 and 19 studies. Significant associations were shown between the presence of the R allele and professional footballer status (OR = 1.35, 95% CI: 1.18-1.53) and the D allele and youth footballers (OR = 1.18, 95% CI: 1.01-1.38). More specifically, the RR genotype (OR = 1.48, 95% CI: 1.23-1.77) and DD genotype (OR = 1.29, 95% CI: 1.02-1.63) exhibited the strongest associations, respectively. These findings may be explained by the association of the RR genotype and DD genotype with power-orientated phenotypes and the relative contribution of power-orientated phenotypes to success in football. As such, the results of this review provide further evidence that individual genetic variation may contribute towards athlete status and can differentiate athletes of different competitive playing statuses in a homogenous team-sport cohort. Moreover, the R577X and I/D polymorphisms are likely (albeit relatively minor) contributing factors that influence athlete status in football.
Topics: Humans; Actinin; Alleles; Genotype; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Soccer
PubMed: 32856541
DOI: 10.1080/02640414.2020.1812195 -
Nutrients Jan 2021Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism ( Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We...
Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism ( Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation.
Topics: Adult; Aged; Alcohol Drinking; Alleles; Breast Neoplasms; Colonic Neoplasms; Diet; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Neoplasms; PPAR gamma; Polymorphism, Genetic; Prostatic Neoplasms; Rectal Neoplasms; Risk Factors
PubMed: 33477496
DOI: 10.3390/nu13010261 -
Journal of Psychiatric Research Nov 2021Ketamine is a dissociative anesthetic used worldwide for anesthesia, pain management, treatment resistant depression (TRD) and suicidality. Predictors of antidepressant... (Review)
Review
Ketamine is a dissociative anesthetic used worldwide for anesthesia, pain management, treatment resistant depression (TRD) and suicidality. Predictors of antidepressant response and adverse effects to ketamine remain poorly understood due to contradictory results. The objective of the systematic review herein is to identify and evaluate the extant literature assessing pharmacogenomic predictors of ketamine clinical benefits and adverse effects. Electronic databases were searched from inception to July 2021 to identify relevant articles. Twelve articles involving 1,219 participants with TRD, 75 who underwent elective surgeries and received ketamine as an anesthetic, 49 with pain, and 68 healthy participants met the inclusion criteria and enrolled to this review. While identified articles reported mixed results, three predictors emerged: 1) Val66Met (rs6265) brain derived neurotrophic factor (BDNF; Met allele) was associated with reduced antidepressant and anti-suicidal effects, 2) CYP2B6*6 (e.g., CYB2B6 metabolizer) was associated with more severe dissociative effects and 3) NET allelic (rs28386840) variant were associated with greater cardiovascular complications (e.g., moderate to severe treatment emergent hypertension). Several important limitations were identified, most notably the small sample sizes and heterogeneity of study design and results. Taken together, preliminary evidence suggests the potential for pharmacogenomic testing to inform clinical practices; however, further research is needed to better determine genetic variants of greatest importance and the clinical validity of pharmacogenomics to help guide ketamine treatment planning.
PubMed: 34844049
DOI: 10.1016/j.jpsychires.2021.11.036 -
The Pharmacogenomics Journal Jul 2022Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the... (Meta-Analysis)
Meta-Analysis
Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the occurrence of a potentially fatal adverse reaction, clozapine-induced agranulocytosis (CIA). Identifying genetic variations contributing to CIA would help predict patient risk of developing CIA and personalize treatment. Here, we (1) review existing pharmacogenomic studies of CIA, and (2) conduct meta-analyses to identify targets for clinical implementation. A systematic literature search identified studies that included individuals receiving clozapine who developed CIA and controls who did not. Results showed that individuals carrying the HLA-DRB1*04:02 allele had nearly sixfold (95% CI 2.20-15.80, p = 0.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, TNFb5, HLA-B*59:01, TNFb4, and TNFd3 showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive HLA-DRB1*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.
Topics: Agranulocytosis; Alleles; Antipsychotic Agents; Clozapine; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 35710824
DOI: 10.1038/s41397-022-00281-9